Eugenia Kumacheva

Properties and emerging applications of self-assembled structures made from inorganic nanoparticles

Just as nanoparticles display properties that differ from those of bulk samples of the same material, ensembles of nanoparticles can have collective properties that are different to those displayed by individual nanoparticles and bulk samples. Self-assembly has emerged as a powerful technique for controlling the structure and properties of ensembles of inorganic nanoparticles. Here we review different strategies for nanoparticle self-assembly, the properties of self-assembled structures of nanoparticles, and potential applications of such structures. Many of these properties and possible applications rely on our ability to control the interactions between the electronic, magnetic and optical properties of the individual nanoparticles.

Patterning surfaces with functional polymers

The ability to pattern functional polymers at different length scales is important for research fields including cell biology, tissue engineering and medicinal science and the development of optics and electronics. The interest and capabilities of polymer patterning have originated from the abundance of functionalities of polymers and a wide range of applications of the patterns. This paper reviews recent advances in top-down and bottom-up patterning of polymers using photolithography, printing techniques, self-assembly of block copolymers and instability-induced patterning. Finally, challenges and future directions are discussed from the point of view of both applicability and strategies for the surface patterning of polymers.

Formation of monodisperse bubbles in a microfluidic flow-focusing device

This letter describes a method for generating monodisperse gaseous bubbles in a microfluidic flow-focusing device. The bubbles can be obtained in a range of diameters from 10 to 1000μm. The volume Vb of the bubbles scales with the flow rate q and the viscosity μ of the liquid, and the pressure p of the gas stream as Vb∝p∕qμ. This method allows simultaneous, independent control of the size of the individual bubbles and volume fraction of the dispersed phase. Under appropriate conditions, bubbles self-assemble into highly ordered, flowing lattices. Structures of these lattices can be adjusted dynamically by changing the flow parameters.

Niche-mediated control of human embryonic stem cell self-renewal and differentiation

Complexity in the spatial organization of human embryonic stem cell (hESC) cultures creates heterogeneous microenvironments (niches) that influence hESC fate. This study demonstrates that the rate and trajectory of hESC differentiation can be controlled by engineering hESC niche properties. Niche size and composition regulate the balance between differentiation‐inducing and ‐inhibiting factors. Mechanistically, a niche size‐dependent spatial gradient of Smad1 signaling is generated as a result of antagonistic interactions between hESCs and hESC‐derived extra‐embryonic endoderm (ExE). These interactions are mediated by the localized secretion of bone morphogenetic protein‐2 (BMP2) by ExE and its antagonist, growth differentiation factor‐3 (GDF3) by hESCs. Micropatterning of hESCs treated with small interfering (si) RNA against GDF3, BMP2 and Smad1, as well treatments with a Rho‐associated kinase (ROCK) inhibitor demonstrate that independent control of Smad1 activation can rescue the colony size‐dependent differentiation of hESCs. Our results illustrate, for the first time, a role for Smad1 in the integration of spatial information and in the niche‐size‐dependent control of hESC self‐renewal and differentiation.

Step-Growth polymerization of inorganic nanoparticles

Nanorod Polymers Nanoparticles and colloids have been used to model crystallization and melting phenomena. Liu et al. (p. 197) studied the polymerization kinetics of nanoparticles. Functionalized arrowhead nanorods acted as linkable units that joined together in solvent-tuned assembly. The results resembled common processes of chemical polymerization: Growth was controlled kinetically and could be interpreted by formulas for step-growth polymerization and branching. Furthermore, some isomerization phenomena were observed, as was the formation of cyclic “macromolecules.” The self-assembly of inorganic nanoparticles exhibits quantifiable behavior similar to step-growth polymerization. Self-organization of nanoparticles is an efficient strategy for producing nanostructures with complex, hierarchical architectures. The past decade has witnessed great progress in nanoparticle self-assembly, yet the quantitative prediction of the architecture of nanoparticle ensembles and of the kinetics of their formation remains a challenge. We report on the marked similarity between the self-assembly of metal nanoparticles and reaction-controlled step-growth polymerization. The nanoparticles act as multifunctional monomer units, which form reversible, noncovalent bonds at specific bond angles and organize themselves into a colloidal polymer. We show that the kinetics and statistics of step-growth polymerization enable a quantitative prediction of the architecture of linear, branched, and cyclic self-assembled nanostructures; their aggregation numbers and size distribution; and the formation of structural isomers.

Control of Human Embryonic Stem Cell Colony and Aggregate Size Heterogeneity Influences Differentiation Trajectories

To better understand endogenous parameters that influence pluripotent cell differentiation we used human embryonic stem cells (hESCs) as a model system. We demonstrate that differentiation trajectories in aggregate (embryoid body [EB])‐induced differentiation, a common approach to mimic some of the spatial and temporal aspects of in vivo development, are affected by three factors: input hESC composition, input hESC colony size, and EB size. Using a microcontact printing approach, size‐specified hESC colonies were formed by plating single‐cell suspensions onto micropatterned (MP) extracellular matrix islands. Subsequently, size‐controlled EBs were formed by transferring entire colonies into suspension culture enabling the independent investigation of colony and aggregate size effects on differentiation induction. Gene and protein expression analysis of MP‐hESC populations revealed that the ratio of Gata6 (endoderm‐associated marker) to Pax6 (neural‐associated marker) expression increased with decreasing colony size. Moreover, upon forming EBs from these MP‐hESCs, we observed that differentiation trajectories were affected by both colony and EB size‐influenced parameters. In MP‐EBs generated from endoderm‐biased (high Gata6/Pax6) input hESCs, higher mesoderm and cardiac induction was observed at larger EB sizes. Conversely, neural‐biased (low Gata6/Pax6) input hESCs generated MP‐EBs that exhibited higher cardiac induction in smaller EBs. Our analysis demonstrates that heterogeneity in hESC colony and aggregate size, typical in most differentiation strategies, produces subsets of appropriate conditions for differentiation into specific cell types. Moreover, our findings suggest that the local microenvironment modulates endogenous parameters that can be used to influence pluripotent cell differentiation trajectories.

Three-dimensional shape transformations of hydrogel sheets induced by small-scale modulation of internal stresses

Although Nature has always been a common source of inspiration in the development of artificial materials, only recently has the ability of man-made materials to produce complex three-dimensional (3D) structures from two-dimensional sheets been explored. Here we present a new approach to the self-shaping of soft matter that mimics fibrous plant tissues by exploiting small-scale variations in the internal stresses to form three-dimensional morphologies. We design single-layer hydrogel sheets with chemically distinct, fibre-like regions that exhibit differential shrinkage and elastic moduli under the application of external stimulus. Using a planar-to-helical three-dimensional shape transformation as an example, we explore the relation between the internal architecture of the sheets and their transition to cylindrical and conical helices with specific structural characteristics. The ability to engineer multiple three-dimensional shape transformations determined by small-scale patterns in a hydrogel sheet represents a promising step in the development of programmable soft matter.

Generation of human embryonic stem cell‐derived mesoderm and cardiac cells using size‐specified aggregates in an oxygen‐controlled bioreactor

The ability to generate human pluripotent stem cell‐derived cell types at sufficiently high numbers and in a reproducible manner is fundamental for clinical and biopharmaceutical applications. Current experimental methods for the differentiation of pluripotent cells such as human embryonic stem cells (hESC) rely on the generation of heterogeneous aggregates of cells, also called “embryoid bodies” (EBs), in small scale static culture. These protocols are typically (1) not scalable, (2) result in a wide range of EB sizes and (3) expose cells to fluctuations in physicochemical parameters. With the goal of establishing a robust bioprocess we first screened different scalable suspension systems for their ability to support the growth and differentiation of hESCs. Next homogeneity of initial cell aggregates was improved by employing a micro‐printing strategy to generate large numbers of size‐specified hESC aggregates. Finally, these technologies were integrated into a fully controlled bioreactor system and the impact of oxygen concentration was investigated. Our results demonstrate the beneficial effects of stirred bioreactor culture, aggregate size‐control and hypoxia (4% oxygen tension) on both cell growth and cell differentiation towards cardiomyocytes. QRT‐PCR data for markers such as Brachyury, LIM domain homeobox gene Isl‐1, Troponin T and Myosin Light Chain 2v, as well as immunohistochemistry and functional analysis by response to chronotropic agents, documented the impact of these parameters on cardiac differentiation. This study provides an important foundation towards the robust generation of clinically relevant numbers of hESC derived cells. Biotechnol. Bioeng. 2009;102: 493–507.

Enhanced electrocatalytic CO2 reduction via field-induced reagent concentration

Electrochemical reduction of carbon dioxide (CO2) to carbon monoxide (CO) is the first step in the synthesis of more complex carbon-based fuels and feedstocks using renewable electricity. Unfortunately, the reaction suffers from slow kinetics owing to the low local concentration of CO2 surrounding typical CO2 reduction reaction catalysts. Alkali metal cations are known to overcome this limitation through non-covalent interactions with adsorbed reagent species, but the effect is restricted by the solubility of relevant salts. Large applied electrode potentials can also enhance CO2 adsorption, but this comes at the cost of increased hydrogen (H2) evolution. Here we report that nanostructured electrodes produce, at low applied overpotentials, local high electric fields that concentrate electrolyte cations, which in turn leads to a high local concentration of CO2 close to the active CO2 reduction reaction surface. Simulations reveal tenfold higher electric fields associated with metallic nanometre-sized tips compared to quasi-planar electrode regions, and measurements using gold nanoneedles confirm a field-induced reagent concentration that enables the CO2 reduction reaction to proceed with a geometric current density for CO of 22 milliamperes per square centimetre at −0.35 volts (overpotential of 0.24 volts). This performance surpasses by an order of magnitude the performance of the best gold nanorods, nanoparticles and oxide-derived noble metal catalysts. Similarly designed palladium nanoneedle electrocatalysts produce formate with a Faradaic efficiency of more than 90 per cent and an unprecedented geometric current density for formate of 10 milliamperes per square centimetre at −0.2 volts, demonstrating the wider applicability of the field-induced reagent concentration concept.

Probing Dynamic Generation of Hot-Spots in Self-Assembled Chains of Gold Nanorods by Surface-Enhanced Raman Scattering

Further progress in the applications of self-assembled nanostructures critically depends on developing a fundamental understanding of the relation between the properties of nanoparticle ensembles and their time-dependent structural characteristics. Following dynamic generation of hot-spots in the self-assembled chains of gold nanorods, we established a direct correlation between ensemble-averaged surface-enhanced Raman scattering and extinction properties of the chains. Experimental results were supported with comprehensive finite-difference time-domain simulations. The established relationship between the structure of nanorod ensembles and their optical properties provides the basis for creating dynamic, solution-based, plasmonic platforms that can be utilized in applications ranging from sensing to nanoelectronics.